The rates of preterm birth and infant mortality have been increasing continuously from 1990 to 2006 and are higher than 29 other countries. Not surprisingly, very-low-birthweight (VLBW, birthweights less than 1500 grams) preterm infants have more health and developmental problems and these problems are more common in male VLBW preterm infants. Male VLBW preterm infants also experience less positive mother-infant interaction, which is problematic because positive mother-infant interactions function as an important protective factor to ameliorate negative health and developmental outcomes associated with prematurity. These associations raise important questions: "What factors beyond gender socialization explain the vulnerability of male VLWB preterm infants to health problems, sub-optimal mother-infant interactions, and poor infant development? Are these factors biological in origin?" Based on well-accepted theories of gender differences with male vulnerability in brain development and social relationships, this study hypothesizes that perinatal testosterone influences infant health and mother- infant interactions by negatively affecting infant cognitive/motor development. The purpose of the proposed project is to explore the potential relationships between perinatal testosterone and;(1) infant health, (2) mother-infant interactions, and (3) infant development based on biological (perinatal testosterone) - stress (perinatal and maternal cortisol) - development (infant cognitive/motor skills) association. If these biological and developmental relationships in mother-VLBW preterm pairs are established, the outcome of the proposed study may highlight the importance of nursing interventions designed to reduce stress among mothers of VLBW preterm infant, especially males. The specific aims of the present study are to determine the relationships between perinatal testosterone levels and: (1) infant health as measured by birthweight, gestational age, Apgar score, presence of health problems, and weight gain (Aim 1), (2) mother-infant interactions after controlling for characteristics of infant (gender and ethnicity) and mother (age, ethnicity, education, and marital status), as well as infant temperament and maternal depressive symptoms (Aim 2), and (3) infant cognitive/motor development after controlling for mother-infant interactions (Aim 3). Biological significance of saliva and plasma testosterone and cortisol levels measured in mother-VLBW preterm infant pairs will be discussed, interpreted, and applied to predict infant development in a collaborative manner amongst the PI, a neonatologist, a pediatric endocrinologist, and a pediatric developmental psychologist. The data from this R21 will lead to further investigations in a future R01 in intervention study. In this all-out effort in the future, we plan to measure the effectiveness of stress-reducing nursing intervention. PUBLIC HEALTH RELEVANCE: The proposed studies are designed to test the hypothesis that prenatal testosterone level is an important biological factor that influence;(1) infant health, (2) mother-infant interactions, and (3) infant cognitive/motor development. Once these biological and developmental relationships in mother and very-low birthweight (VLBW) preterm infant pairs are established, the outcomes of the study may highlight the importance of nursing interventions designed to reduce stress among mothers of VLBW preterm infants, especially males.